Prevention of multiple pregnancies in couples with unexplained or mild male subfertility

A randomized trial to evaluate whetherMNC-IVF or IVF-eSET reduces multiple pregnancies as compared to IUI-COH in couples with unexplained subfertility or mild male subfertility and poor fertility prospects.

Currently couples with unexplained or mild male subfertility and a poor prognosis (chance of spontaneous pregnancy < 30 % as calculated by the validated model of Hunault) are treated with intra uterine insemination (IUI) and controlled ovarian hyperstimulation (COH). After 6 cycles of unsuccessful IUI-COH, these couples are subsequently treated with in vitro fertilisation (IVF)and double embryo transfer (DET).

With this treatment 10-20% of the achieved pregnancies is multiple pregnancy.

These are high risk pregnancies with regard to the obstetrics and the neonatal outcomes. Premature birth, growth retardationand pre eclampsia are the most frequent complications. These result higher medical costs.

It is unclear whether alternative treatments such as modified natural cycle MNC-IVF, or IVF with elective single embryo transfer(eSET) for this population selection result in comparable pregnancy rates, and simultaneously reduce the number of multiple pregnancies. Generally, patients consider IVF as a more intense treatment than IUI.

Objective

Our main objective is to prevent multiple pregnancies and the concomitant neonatal mortality and morbidity while retaining acceptable delivery rates in couples with unexplained subfertility or mild subfertility with poor fertility. Furthermore, we intend to evaluate the preference of couples for the treatments and assess how couples value a twin as outcome, compared to a singleton pregnancy or no pregnancy. Also the costs of the treatment, follow up, delivera an maternal and perinatal hospital care untile six weeks after delivery are evaluated.

Study Design

The study design is a multi centred randomized clinical trial

Population

Couples with unexplained infertility or mild male infertility with poor fertilitity prospects. Poor fertility prospects are defined as failure to conceive within at least 3 years of unprotected intercourse or a chance of spontaneous pregnancy below 30% within 12 months as calculated by Hunault. Female age must be between 18 and 38 years.

Intervention

·Intra uterine insemination (IUI) with stimulation

·In Vitro Fertilisation with transfer of one embryo (IVF-eSET)

·In Vitro Fertilisation with a modified natural cycle (IVF-MNC)

Randomisation (lottery) will determine whether a couple will start with either

6 stimulated IUI cycles or 3 IVF e SETcycles or 6 IVF MNC cycles.

Outcomes

Primary outcome measurements in all groups is life birth of a child. Secondary outcomes are multiple pregnancies, clinical pregnancies, pregnancy complications such as pre-eclampsia, and a cost analysis and patient satisfaction.